Natural products and their semi-synthetic derivatives are used widely in cancer chemotherapy (Newman D J and Cragg G M. J. Nat. Prod. 2012, 75, 311-335; Kinghorn A D et al. Pure Appl. Chem. 2009, 81, 1051-1063). As an example, etoposide (VP-16) is a semi-synthetic aryltetralin lignan glycoside modeled on the natural product podophyllotoxin. It targets DNA topoisomerase II (topo II) and has been utilized for decades to treat several types of cancer (Meresse P et al. Curr. Med Chem. 2004, 11, 2443-2466). However, side effects have been reported for etoposide, including myelosuppression and the development of secondary leukemias linked to topo II inhibitory activity (Ezoe S. Int. J. Environ. Res. Public Health 2012, 9, 2444-2453).
Podophyllotoxin is an aryltetralin lignan that occurs in Podophyllum peltatum and P. emodi var. hexandrum (syn. Sinopodophyllum hexandrum) (Berberidaceae) (Meresse P et al. Curr. Med Chem. 2004, 11, 2443-2466; Chattopadhyay S et al. Nat. Prod Res. 2004, 18, 51-57; Girl A and Narasu M L. Cytotechnology 2000, 34, 17-26). In addition to Podophyllum species (Atta-ur-Rahman et al. Phytochemistry 1995, 40, 427-431), a number of arylnaphthalene lignan lactones, structurally similar to podophyllotoxin, have been identified as minor constituents from plants in the genera Cleistanthus (Euphorbiaceae) (Pinho P M M and Kijjoa A Phytochem. Rev. 2007, 6, 175-182), Haplophyllum (Rutaceae) (Oozier B et al. Phytochemistry 1996, 42, 689-693; Al-Abed Y et al. Phytochemistry 1998, 49, 1779-1781), Justicia (Acanthaceae) (Susplugas S et al. J. Nat. Prod. 2005, 68, 734-738), Mananthes (Acanthaceae) (Tian J et al. Helv. Chim. Acta 2006, 89, 291-298), and Phyllanthus (Phyllanthaceae) (Lin M T et al. J. Nat. Prod. 1995, 58, 244-249; Tuchinda P et al. Planta Med. 2006, 72, 60-62; Wu S J and Wu T S. Chem. Pharm. Bull. 2006, 54, 1223-1225; Tuchinda P et al. J. Nat. Prod 2008, 71, 655-663; Wang C Y et al. Phytochem. Anal. 2011, 22, 352-360). Many naturally occurring arylnaphthalene lignan lactones have been reported to possess cytotoxicity toward panels of human cancer cell lines (Susplugas S et al. J. Nat. Prod. 2005, 68, 734-738; Lin M T et al. J. Nat. Prod. 1995, 58, 244-249; Tuchinda P et al. Planta Med. 2006, 72, 60-62; Wu S J and Wu T S. Chem. Pharm. Bull. 2006, 54, 1223-1225; Tuchinda P et al. J. Nat. Prod 2008, 71, 655-663; Wang C Y et al. Phytochem. Anal. 2011, 22, 352-360; Fukamiya N and Lee K H. J. Nat. Prod. 1986, 49, 348-350; Novelo M et al. J. Nat. Prod. 1993, 56, 1728-1736; Day S H et al. J. Nat. Prod. 1999, 62, 1056-1058; Innocenti G et al. Chem. Pharm. Bull. 2002, 50, 844-846; Day S H et al. J. Nat. Prod 2002, 65, 379-381; Ramesh C et al. Chem. Pharm. Bull. 2003, 51, 1299-1300; Vasilev N et al. J. Nat. Prod. 2006, 69, 1014-1017), and several of their synthetic analogues also showed such activity (Zhao Y et al. Arch. Pharm. Chem. Life Sci. 2012, 345, 622-628; Shi D K et al. Eur. J. Med. Chem. 2012, 47, 424-431). Some arylnaphthalene lignan lactones have exhibited in vivo antitumor efficacy (Rezanka T et al. Phytochemistry 2009, 70, 1049-1054; Kang K et al. Neoplasia 2011, 13, 1043-1057), and a compound, cleistanthin B, showed selective cytotoxicity toward human tumor cells (Kumar C P P et al. Mutagenesis 1996, 11, 553-557). Some of these compounds showed a mechanism of action different from etoposide (Susplugas S et al. J. Nat. Prod. 2005, 68, 734-738; Kang K et al. Neoplasia 2011, 13, 1043-1057), and several analogues did not act as topo II poisons mechanistically (Zhao Y et al. Arch. Pharm. Chem. Life Sci. 2012, 345, 622-628; Shi D K et al. Eur. J. Med. Chem. 2012, 47, 424-431). What are needed are new compositions for the treatment of cancer, e.g., arylnaphthalene lactone derivatives. The compounds, compositions and methods disclosed herein address these and other needs.